UESPA (pronounced "you-spah") was first mentioned in abbreviated form in TOS: "Charlie X" and the acronym was spelled out in TOS: "Tomorrow is Yesterday". It was one of several names given in early episodes for the agency under which the Enterprise and its crew operated before writers finally settled on "Starfleet" (also formatted as "Star Fleet").

In the script of "From the First Day to the Last, Part II" (a developmental precursor to TOS: "The Menagerie, Part II"), UESPA was mentioned at a hearing to determine whether to allow Christopher Pike to return to Talos IV to die there. At the hearing, Captain Kirk stated, "UESPA regulations dictate that any data directly or indirectly connected with alien behavior, customs or physical aspects be placed in the captain's log at his earliest opportunity after an encounter with those aliens... this to add to the body of knowledge in our space probe records." Commander Jermane, an officer who was objecting to Pike's request, considered this an "almost verbatim" recital from UESPA regulations.

In the final draft script of "The Menagerie", Starbase 11 (then called "Star Base 811") was described as being identified, in signage intended to appear on-screen, as a "United Space Agency" facility, even though the name "Starfleet" had been devised by then.

In "Tomorrow is Yesterday", Captain Kirk refers to UESPA as a "combined service," but he is vague enough that it is more likely that he was actually referring to his Starfleet crew. It is possible that starship crews of his time were a combined service of both the naval ranked Starfleet and the military ranked UESPA officers. This would explain the use of military ranks in "The Cage". This may also explain West's rank of colonel in Star Trek VI: The Undiscovered Country. The same possibility would also seem to be implied by the appearance of the joint Starfleet Command/UESPA seal in "Demons".